Synthetic Evidence of the Amadori-Type Alkylation of Biogenic Amines by the Neurotoxic Metabolite Dopegal

J Org Chem. 2020 Jan 17;85(2):1202-1207. doi: 10.1021/acs.joc.9b01948. Epub 2019 Dec 30.

Abstract

The neurotransmitter metabolite 3,4-dihydroxy-phenylglycolaldehyde (dopegal) damages neurons and the myocardium by protein cross-linking, resulting in conglomerations and cell death. We investigated this process on a synthetic scale, leading to the discovery of an Amadori-type rearrangement of dopegal in the reaction with several amino acids and neuropeptides. This alkylation also occurs with neurotransmitters, suggesting an influence of dopegal on neurochemical processes. The rearrangement occurs readily under physiological conditions.

MeSH terms

  • Acetaldehyde / analogs & derivatives*
  • Acetaldehyde / chemistry
  • Acetaldehyde / toxicity
  • Alkylation
  • Biogenic Amines / chemistry*
  • Nervous System / drug effects
  • Neurotransmitter Agents / chemistry*
  • Neurotransmitter Agents / toxicity
  • Spectrum Analysis / methods

Substances

  • Biogenic Amines
  • Neurotransmitter Agents
  • dopegal
  • Acetaldehyde